The objectives of these studies are to elucidate the role of brain monoamines in the regulation of luteinizing hormone (LH) and prolactin secretion, and to utilize this information for the pharmacological control of mammary tumors. We previously demonstrated that complete deafferentation of the medial basal hypothalamus (MBH) caused a total disappearance of norepinephrine (NE) without affecting the dopamine (DA) content within the MBH. Using the highly sensitive radiochemical catecholamine-o-methyl transferase assay for NE and DA we have confirmed these earlier findings on single deafferented MBH. Direct electrical stimulation of the deafferented MBH will be performed to stimulate or inhibit LH and prolactin release. Serum and pituitary LH and prolactin levels will be measured using the NIAMD rat radioimmunoassays. The role of dopaminergic neurons in these responses will be pharmacologically tested. The endogenous dopamine pool will be labeled with intraventricularly administered H3-tyrosine. Changes in the metabolism of dopamine-containing neurons isolated within the deafferented island will be directly correlated with the alpha-MPT induced changes in prolactin secretion. The post-ovariectomy rise in LH is only partially blocked by complete deafferentation. Estrogen and progesterone will be administered to these animals in order to study the site of negative feedback of LH secretion. The role of dopaminergic neurons in steroid feedback will be determined using pharmacological agents which potentiate, or inhibit, dopaminergic activity. Studies will be performed to attempt to measure DA levels in the cavernous sinus blood of awake dogs and to correlate these levels with prolactin secretion.